June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
HMGA2 regulates the self-renewal of retinal progenitors
Author Affiliations & Notes
  • Sowmya Parameswaran
    Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, NE
  • Iqbal Ahmad
    Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, NE
  • Footnotes
    Commercial Relationships Sowmya Parameswaran, None; Iqbal Ahmad, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 2214. doi:
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      Sowmya Parameswaran, Iqbal Ahmad; HMGA2 regulates the self-renewal of retinal progenitors. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2214.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: Retinal progenitors unlike neural stem cells do not self-renew under normal culture conditions in vitro. Our recent study demonstrates that retinal progenitors can self-renew, but this property is non-cell autonomous, requiring interactions with other cell types. Here, we have examined the role of non-histone chromosomal high-mobility group protein A2; HMGA2 in the self-renewal.

Methods: HMGA2 expression was determined by Q-PCR, immunohistochemistry and Western analysis in embryonic day 18 (E18) progenitors. Its involvement in self-renewal of E18 progenitors was determined by neurosphere assay in the presence of conditioned medium obtained from cultured endothelial cells (ECCM) and Hmga2 siRNA.

Results: To determine the physiological relevance of HMGA2 in retina, we analyzed its temporal expression by Q-PCR, which revealed a temporal decrease in Hmga2 expression during retinal development in vivo. Analysis of spatial localization of HMGA2 by immunohistochemistry on E18 retinal sections showed a center to peripheral gradient of HMGA2 distribution, co-localized with BrdU positive progenitors. Involvement of HMGA2 in self-renewal of retinal progenitors was examined in ECCM generated neurospheres. A significant increase in Hmga2 transcript levels and Hmga2+ BrdU+ cells was observed in ECCM generated neurospheres compared to EGF controls. To determine whether Hmga2 regulatory axis is involved in ECCM mediated self - renewal, HMGA2 expression was attenuated using siRNA lentivirus in E18 retinal dissociates. HMGA2 knockdown led to decrease in the number of neurospheres and BrdU positive cells suggesting the loss of self-renewal. Data on HMGA2 axis involved in self-renewal of retinal progenitors will be provided.

Conclusions: Retinal progenitors display a non-cell autonomous self-renewal property, which is likely to be regulated by a molecular axis, underpinned by HMGA2.

Keywords: 688 retina • 721 stem cells  
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